小干扰RNA的非病毒载体:从实验室走向临床

Non-viral Vectors for Small Interference RNA Delivery: from Bench to Bedside

小干扰RNA(si RNA)作为RNA干扰技术的重要效应分子,具有治疗多种疾病的巨大潜力。目前已有3款si RNA药物获得美国食品药品监督管理局批准上市,数十款si RNA药物处于临床试验阶段。脂质纳米颗粒、N-乙酰半乳糖胺(Gal NAc)-si RNA共轭物、高分子聚合物以及仿生载体等非病毒载体为解决si RNA体内易降解、易清除、免疫原性以及细胞膜渗透能力弱等问题提供了良好的解决策略。随着对疾病基因谱和非病毒载体的不断深入研究,越来越多的si RNA药物进入临床前和临床试验研究。文中对si RNA药物发展历程、体内应用过程中的生物学屏障、递送载体结构与功能进行系统梳理,以期对si RNA药物的未来发展提供借鉴。

As one of the important effector molecules of RNA interference, small interference RNA(siRNA) has great potential to treat a variety of diseases. At present, three siRNA drugs have been approved by the Food and Drug Administration, and dozens of siRNA drugs are in clinical trials. Non-viral vectors such as lipid nanoparticle, N-acetylgalactosamine(Gal NAc)-si RNA conjugate, polymer and biomimetic vector provide good solutions to the problems of easy degradation and clearance of siRNA in vivo, immunogenicity and weak permeability of cell membrane. With the deepened study of disease gene spectrum and non-viral vector, more and more siRNA drugs have entered preclinical studies and clinical trials. This paper systematically reviews and analyzes the development process of siRNA drugs, biological barriers in the process of in vivo application and the structure and function of delivery carriers, in order to provide reference for the future development of siRNA drugs.